Caged agonist of P2Y1 and P2Y12 receptors for light-directed facilitation of platelet aggregation

Biochemical Pharmacology
Zhan-Guo GaoKenneth A Jacobson

Abstract

We have prepared a caged form (MRS2703) of a potent dual agonist of the P2Y(1) and P2Y(12) nucleotide receptors, 2-MeSADP, by blocking the beta-phosphate group with a 1-(3,4-dimethyloxyphenyl)eth-1-yl phosphoester. Although MRS2703 is itself inactive at human P2Y(1) and P2Y(12) receptors expressed heterologously in 1321N1 astrocytoma cells or in washed human platelets, this derivative readily regenerates the parent agonist upon mild irradiation with long-wave UV light (360 nm). The functional effect of the regenerated agonist was demonstrated by a rise in intracellular calcium mediated by either P2Y(1) or P2Y(12) receptors in transfected cells. Washed human platelets exposed to a solution of MRS2703 were induced to aggregate upon UV irradiation. At 1.0 microM MRS2703, full aggregation was achieved within 1 min of irradiation. Thus, this caged nucleotide promises to be a useful probe for potent P2Y receptor activation with light-directed spatial and temporal control.

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Citations

Apr 13, 2011·Purinergic Signalling·Kenneth A JacobsonStefano Costanzi
Sep 4, 2010·Pharmacological Research : the Official Journal of the Italian Pharmacological Society·Zhan-Guo GaoKenneth A Jacobson
Dec 22, 2015·Neuropharmacology·Kenneth A Jacobson, Christa E Müller
Nov 19, 2008·Physical Chemistry Chemical Physics : PCCP·Alexey V CherepanovHuub J M De Groot
Apr 4, 2015·Molecular Pharmacology·Kenneth A JacobsonEvgeny Kiselev
Jul 9, 2020·Biomedical Optics Express·Darya V SpiryovaAlexander E Moskalensky
Jun 23, 2021·Purinergic Signalling·Tao WangYong Tang
Apr 26, 2018··Oleg Y. KarmatskihAlexei Y. Vorob'ev

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